dorsomorphin chemical structureStemolecule Dorsomorphin dihydrochloride is a potent inhibitor of AMPactivated protein kinase (AMPK) (Ki=109nM) and bone morphogenic protein(BMP) signaling. Dorsomorphin was identified in a screen for compounds that perturb dorsoventral axis formation in zebrafish. Dorsomorphin functions through inhibition of BMP type I receptors ALK2, ALK3 and ALK6 and thus blocks BMP-mediated SMAD1/5/8 phosphorylation3. BMP signaling coordinates developmental patterning and have essential physiological roles in mature organisms. Dorsomorphin has been used to probe BMP signaling in ironhepcidin homeostasis, cardiomyogenesis and steogenesis.

  • QUESTION: How was Dorsomorphin discovered?

ANSWER: In 2007, Charles Hong, M.D., Ph.D., and colleagues described using fish embryos to screen for compounds that interfere with signaling pathways involved in early development - pathways known to play roles in a variety of disease processes. They discovered the compound "dorsomorphin" and demonstrated that it blocked BMP (bone morphogenetic protein) signaling, which has been implicated in anemia, inflammatory responses and bone-related disorders.

  • QUESTION: Is there alternative name?
    ANSWER: Yes, 6-[4-(2-Piperidin-1-yl)-ethoxy)-phenyl)]-3-pyridin-4-yl- pyrazolo[1,5-a]-pyrimidine;

Compound C.

  • QUESTION: What is the basic chemical data:
    ANSWER: Chemical Formula: C24H25N5O, CAS Number: 866405-64-3, Appearance: Light yellow

solid, Molecular Weight: 399.49.

  • QUESTION: What is Dorsomorphin's solubility?

ANSWER: For a 10 mM concentrated stock solution of Dorsomorphin, reconstitute the compound by adding 407.8 l of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37°C for 2 to 5 minutes. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. This molecule is soluble in DMSO at 100 mM and water at 100 mM.

  • QUESTION: What are storage and stability of Dorsomorphin? ANSWER: Store powder at 4°C protected from light. Following reconstitution, store aliquots at -20°C.

Stock solutions are stable for 6 months when stored as directed.

  • QUESTION: What is Dorsomorphin's quality control?

ANSWER: The purity of Dorsomorphin was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of Dorsomorphin was tested on mouse embryonic stem cells.

Source: Gao, Y., Zhou, Y., Xu, A., and Wu, D. (2008) Effects of an AMP-activated, protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells. Biol Pharm Bull 31: 1716-1722. 2. Anderson, G.J., and Darshan, D. (2008) Small-molecule dissection of BMP signaling. Nat Chem Biol 4: 15-16. Product Specification Sheet©Stemgent 2009 —¦ For research use only. Not for diagnostic use. Stemgent —¦ 10575 Roselle St. San Diego, CA 92121—¦ 1.617.245.0000 —¦ www.stemgent.com v1.0, Yu, P.B., Hong, C.C., Sachidanandan, C., Babitt, J.L., Deng, D.Y., Hoyng, S.A. Lin, H.Y., Bloch, K.D., and Peterson, R.T. (2008) Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 4:33-41. Heisenberg, C.P., and Solnica-Krezel, L. (2008) Back and forth between cell fate specification and movement during vertebrate gastrulation. Curr Opin Genet Dev 18: 311- 316. Cain, J.E., Hartwig, S., Bertram, J.F., and Rosenblum, N.D. (2008) Bonemorphogenetic protein signaling in the developing kidney: present and future. Differentiation 76: 831-842. Hao, J., Daleo, M.A., Murphy, C.K., Yu, P.B., Ho, J.N., Hu, J., Peterson, R.T. Hatzopoulos, A.K., and Hong, C.C. (2008) Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS ONE 3: e2904. Seib, F.P., Franke, M., Jing, D., Werner, C., and Bornhauser, M. (2009) Endogenous bone morphogenetic proteins in human bone marrow-derived multipotent mesenchymal stromal cells. Eur J Cell Biol 88: 257-271., Wikipedia.

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  1. Dorsomorphin Inhibit Myostatin / GDF8 Signaling, inhibits Bmp-Smad pathway
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